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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Research Article

Simultaneous Method Development and Validation of Anastrozole Along with Piperine: Degradation Studies and Degradants Characterization Using LC-QTOF-ESI-MS Along with In-silico ADMET Predictions

Author(s): K. Jony Susanna, Rahul Gajbhiye, Bhaskar Sarmah, Sachin Dattram Pawar, Pakhuri Mehta, Upadhyayula Suryanarayana Murty, V. Ravichandiran, Amit Alexander and Pramod Kumar*

Volume 23, Issue 2, 2022

Published on: 11 April, 2022

Page: [113 - 130] Pages: 18

DOI: 10.2174/1389200223666220215152606

Price: $65

Abstract

Background: Anastrozole (ATZ) is a selective non-steroidal inhibitor widely used for the treatment of breast cancer in post-menopausal women. ATZ exerts its biological activity by inhibiting the enzyme aromatase, which is responsible for converting androgens to estrogens. Piperine (PIP), a natural alkaloid and the main component of black pepper, is used as a bioenhancer and for combating a variety of health issues ranging from upset stomach to dental problems.

Introduction: ATZ has been reported to have poor water solubility and less bioavailability. The novel combination of ATZ and PIP was proposed to enhance the bioavailability of both the compounds. However, there are no reported studies on the simultaneous estimation of ATZ and PIP as well as stability studies to explore their potential interactions and degradation profiling.

Method: A simple, accurate, precise, robust, sensitive, reliable, and economic analytical method for the simultaneous estimation of ATZ and PIP was developed using acetonitrile and water (60:40) as the mobile phase. Forced degradation studies and characterization of degradants were performed, and degradants were identified for molecular weight using LC-QTOF-ESI-MS; the structures of degradants were confirmed with mass accuracy measurements. The mechanism of each degradant has also been described in more detail in the manuscript.

Results and Conclusion: A total of fourteen degradants were characterized and reported for their good human oral absorption. A precise, robust, accurate, cheap, and sensitive RP-HPLC-DAD simultaneous method for the estimation of ATZ and PIP has been developed. From the future point of view, there is huge scope to conduct pharmacological, pharmacodynamic, and drug-herb interaction studies based on this fruitful outcome. All the degradants may be screened against MDR-resistant breast cancer in the future to check their potential as a drug target.

Keywords: Isosbestic point, RP-UHPLC-DAD, stability studies, LC-QTOF-ESI-MS, and ADMET.

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